Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.
Sci Rep. 2017 May 15;7(1):1882. doi: 10.1038/s41598-017-02109-0.
The herpes simplex virus (HSV) UL31 gene encodes a conserved member of the herpesvirus nuclear egress complex that not only functions in the egress of DNA containing capsids from the nucleus, but is also required for optimal replication of viral DNA and its packaging into capsids. Here we report that the UL31 protein from HSV-2 can be recruited to sites of DNA damage by sequences found in its N-terminus. The N-terminus of UL31 contains sequences resembling a poly (ADP-ribose) (PAR) binding motif suggesting that PAR interactions might mediate UL31 recruitment to damaged DNA. Whereas PAR polymerase inhibition prevented UL31 recruitment to damaged DNA, inhibition of signaling through the ataxia telangiectasia mutated DNA damage response pathway had no effect. These findings were further supported by experiments demonstrating direct and specific interaction between HSV-2 UL31 and PAR using purified components. This study reveals a previously unrecognized function for UL31 and may suggest that the recognition of PAR by UL31 is coupled to the nuclear egress of herpesvirus capsids, influences viral DNA replication and packaging, or possibly modulates the DNA damage response mounted by virally infected cells.
单纯疱疹病毒 (HSV) UL31 基因编码疱疹病毒核出芽复合物的保守成员，该复合物不仅在含有 DNA 的衣壳从核中出芽的过程中发挥作用，而且对于病毒 DNA 的最佳复制及其包装到衣壳中也是必需的。在这里，我们报告 HSV-2 的 UL31 蛋白可以通过其 N 端的序列被募集到 DNA 损伤部位。UL31 的 N 端包含类似于聚（ADP-核糖）（PAR）结合基序的序列，这表明 PAR 相互作用可能介导 UL31 募集到受损 DNA。虽然 PAR 聚合酶抑制阻止了 UL31 募集到受损 DNA，但通过共济失调毛细血管扩张突变的 DNA 损伤反应途径的信号转导抑制没有影响。这些发现进一步通过使用纯化组件证明 HSV-2 UL31 和 PAR 之间直接和特异性相互作用的实验得到支持。这项研究揭示了 UL31 的一个先前未被识别的功能，并且可能表明 UL31 通过 PAR 的识别与疱疹病毒衣壳的核出芽偶联，影响病毒 DNA 复制和包装，或者可能调节病毒感染细胞所引发的 DNA 损伤反应。
